[PDF][PDF] Inflammation directs memory precursor and short-lived effector CD8+ T cell fates via the graded expression of T-bet transcription factor

NS Joshi, W Cui, A Chandele, HK Lee, DR Urso… - Immunity, 2007 - cell.com
NS Joshi, W Cui, A Chandele, HK Lee, DR Urso, J Hagman, L Gapin, SM Kaech
Immunity, 2007cell.com
As acute infections resolve, effector CD8+ T cells differentiate into interleukin-7 receptor lo
(IL-7R lo) short-lived effector cells (SLECs) and IL-7R hi memory precursor effector cells
(MPECs) capable of generating long-lived memory CD8+ T cells. By using another SLEC
marker, KLRG1, we found that KLRG1 hi effector cells began appearing early during
infection and were committed to downregulating IL-7R. Unlike IL-7R hi MPECs, KLRG1 hi IL-
7R lo SLECs relied on IL-15, but IL-15 could not sustain their long-term maintenance or …
Summary
As acute infections resolve, effector CD8+ T cells differentiate into interleukin-7 receptorlo (IL-7Rlo) short-lived effector cells (SLECs) and IL-7Rhi memory precursor effector cells (MPECs) capable of generating long-lived memory CD8+ T cells. By using another SLEC marker, KLRG1, we found that KLRG1hi effector cells began appearing early during infection and were committed to downregulating IL-7R. Unlike IL-7Rhi MPECs, KLRG1hi IL-7Rlo SLECs relied on IL-15, but IL-15 could not sustain their long-term maintenance or homeostatic turnover. The decision between SLEC and MPEC fates was regulated by the amount of inflammatory cytokines (i.e., IL-12) present during T cell priming. According to the amount of inflammation, a gradient of T-bet was created in which high T-bet expression induced SLECs and low expression promoted MPECs. These results elucidate a mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8+ T cells and, correspondingly, regulates their memory cell potential.
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